pH-independent immediate release polymethacrylate formulations--an observational study

Area of Science:

• Pharmaceutical Technology
• Polymer Science

Background:

• Eudragit® E PO (EudrE) is a pH-sensitive polymethacrylate commonly used in drug delivery.
• Developing pH-independent formulations is crucial for consistent drug release across physiological pH variations.
• Ibuprofen (IBP) is a widely used non-steroidal anti-inflammatory drug.

Purpose of the Study:

• To develop a pH-independent immediate release dosage form of ibuprofen (IBP) using Eudragit® E PO (EudrE).
• To investigate two strategies: chemical modification (quaternization) of EudrE and addition of dicarboxylic acids.
• To assess the impact of these modifications on IBP release profiles and formulation stability.

Main Methods:

• Hot melt extrusion and injection molding were used to produce biconvex tablets.
• In vitro dissolution studies were conducted at various pH levels (1, 3, and 5).
• Chemical modification involved quaternization of the amine function in EudrE; physical modification involved adding succinic, glutaric, or adipic acid.

Main Results:

• A minimum of 25% quaternization of EudrE partially eliminated pH-dependent drug release up to pH 5.
• Addition of dicarboxylic acids, particularly 20 wt.% succinic acid, significantly enhanced IBP release at pH 5 (from 0% to 92% in 1 hour).
• Both methods yielded pH-independent (up to pH 5) immediate release formulations, but stability issues (API recrystallization) and mechanical instability were observed.

Conclusions:

• Both polymer quaternization and dicarboxylic acid addition can achieve pH-independent immediate release of ibuprofen up to pH 5 using Eudragit® E PO.
• Stability and mechanical integrity challenges need to be addressed for successful clinical application.
• Further research is required to optimize these approaches for a robust pH-independent formulation.